A key problem in sensory neuroscience is how nervous systems can detect objects of interest in noisy and cluttered sensory scenes, which then guide further action. This ability to pick out important information from the array of mixed stimuli is thought to involve extensive top-down modulation that interacts with feedforward processing of information. We propose to investigate this important function in the olfactory system of behaving mice using optogenetic and optophysiological methods. Olfaction is critical for the survival of many animals, which use this sense for to find food and mates, and to avoid predators. Information about volatile odorants sensed by olfactory sensory neurons is passed on to the olfactory bulb (OB), whose output reaches many cortical directly areas. This feedforward architecture is disrupted by massive feedback connections throughout the olfactory system, which are thought to provide context and learning-related signals to aid in odor perception. We recently developed an odor-guided behavioral task in which mice are required to parse complex odorous stimuli. In this project, we will use this exciting new behavioral assay to examine the role of cortical feedback to the OB in the genetically-accessible mouse model. To achieve our goals, we will first characterize how complex odor mixtures are represented in the OB, and then examine the effects of selective optogenetic perturbation of cortical feedback projections on the coding of complex odor stimuli in the OB. Then using a suite of cutting-edge methods already established in our group, we will uncover how the feedback signals conveyed to the OB evolve as mice learn to perform this task. Experiments in this project will be guided by three Aims. Aim 1: To determine how the output neurons of the OB represent odorant mixtures and how they are altered after mice learn the mixture task. Aim 2: To determine the effects of selective optogenetic perturbation of olfactory cortical neuron activity on odor coding in OB output neurons. Aim 3: To determine the features of stimulus-related signals carried by cortical feedback axons to the OB in nave mice and in mice that have learnt the mixture task. The research proposed has broad relevance for neuroscience because it will shed light on how brains interpret ambiguous sensory stimuli in cluttered environments, an ability that is thought to involve top-down feedback. This ability is thought to be impaired with aging, as well as in some mental disorders. Therefore, understanding this process in the normal brain could help devise specific and efficacious treatments in abnormal conditions.